Pacylex Pharmaceuticals is expanding its cancer treatment research by presenting novel insights into N-myristoyltransferase inhibitors (NMTis) as potential payloads for antibody drug conjugates (ADCs) at the 2nd Annual ADC Payload Summit in Boston, Massachusetts.
The pharmaceutical company's research highlights a significant challenge in current ADC development: the limited number of payloads effectively killing cancer cells. NMT inhibitors represent a promising alternative, demonstrating the ability to simultaneously disrupt multiple critical processes in cancer cell growth and survival.
In preclinical studies, NMT inhibitors have shown remarkable potential in regressing solid tumor cancers when used as ADC payloads. Pacylex holds an exclusive license to 503 NMTis, with 28 compounds displaying potent single-digit nanomolar inhibition capabilities against human NMT1.
The company's lead compound, zelenirstat, has already demonstrated promising clinical results. In a Phase 1 study involving 24 heavily pretreated patients with non-Hodgkin's lymphoma and solid tumors, the drug was well-tolerated with no dose-limiting toxicities. Notably, patients receiving the recommended Phase 2 dose experienced significantly better progression-free and overall survival rates.
One particularly encouraging outcome was a Phase 2a patient with diffuse large B-cell lymphoma achieving a partial response and partial metabolic response while on zelenirstat. Currently, the company is conducting additional studies in acute myeloid leukemia patients.
CEO Michael Weickert emphasized the potential of their research, highlighting the strong correlation between genes predicting sensitivity to zelenirstat and ADC targets. This correlation suggests NMTis could be effective in targeting and eliminating cancer cells that are currently challenging to treat.
The research presents a potential paradigm shift in cancer treatment, offering a more nuanced approach to targeting cancer cells by disrupting multiple cellular processes simultaneously. By focusing on inhibiting myristoylation—a critical protein modification process—NMTis could provide a novel mechanism for interrupting cancer cell growth and survival.
As the pharmaceutical industry continues to seek more effective cancer treatments, Pacylex's research into NMT inhibitors represents a promising avenue for future therapeutic strategies. The company's comprehensive approach and early clinical success suggest that these compounds could become a significant tool in oncology's ongoing battle against complex and resistant cancers.
